Nicotinic receptor dysfunction and impaired semantic memory occur early in Alzheimer's disease patients (AD). Previous research implied that nicotine's ability to enhance alertness, arousal, and cognition in a number of nonclinical populations was a function of its ability to stimulate CNS nicotinic cholinergic receptors. In this study it was hypothesized that transdermal administration of nicotine would increase both regional cerebral glucose metabolism (rCMRglc) and semantic memory (as assessed by verbal fluency). Two mild AD and two elderly controls underwent positron emission tomography scanning during a double blind nicotinic agonist verbal fluency challenge procedure. rCMRglc increases occurred in both AD patients, but not controls. In the two AD patients, verbal fluency scores increased by an average of 17%. One elderly control's verbal fluency increased, and the other decreased. These findings suggest that nicotine's effect on metabolism and verbal fluency is due to its ability to stimulate the cholinergic system.

Positron emission tomography (PET) has dramatically improved our ability to examine the functioning of the living brain. PET studies of neural pathways of the major sensory modalities--auditory, visual, somatosensory--have confirmed many traditional neuropsychological concepts, such as cross-lateral representation and regional functioning to particular primary sensory cortical areas. Other PET studies have used radioisotopes to examine relationships between radiopharmaceutical agents and neurobehavioral functioning in both normal and neuropathological states. In some areas, PET methodology requires further refinement. For example, effort should be made to develop the technology to do multiple scans within a short time frame; statistical procedures to examine relationships between neuropsychological tasks and the activity or presence of radiopharmaceutical agents in multiple sites; adequate controls for experimental error; and activation paradigms controlling the nonspecific effects of simple arousal. PET activation models of cognition suggest that a "systems efficiency" approach to assessing neuropsychological test performance involving both serial and parallel processing would be useful. These developments will improve empirical methodology and our understanding of brain-behavior relationships.